The biochemical interaction of insulin and epidermal growth factor (EGF) with human breast cancer cells has been investigated. Certain cell lines respond to these hormones with enhanced proliferation; others do not. However, all lines examined have specific receptors for these factors. In addition, all lines internalize the hormone-receptor complex and degrade the hormones to small peptide fragments. In the cells that respond to the hormones there is a progressive loss in the ability to dissociate the hormone from the cells as the time of association increases. We are currently characterizing this difference in more detail since it may provide clues to the mechanism of action of these hormones.